1. Field of the Invention
This invention relates to new and useful 1-N-(.omega.-aminoalkanesulfonyl) derivatives of aminoglycosidic antibiotics and a process for the preparation thereof.
2. Description of the Prior Art
The synthesis of 1-amino-substituted derivatives of aminoglycosidic antibiotics which are active to bacteria resistant to such aminoglycosidic antibiotics and therapeutically useful due to the presence of the substituent in the 1-amino group has been preceded by butirosins A and B which are aminoglycosidic antibiotics bearing (S)-.alpha.-hydroxy-.gamma.-aminobutyryl substituent on the 1-amino group discovered as a fermentative product of natural origin (see U.S. Pat. No. 3,541,078 where the butirosins are referred to as ambutirosins A and B). Substantial success has been achieved by the synthesis of amikacin, 1-N-(.alpha.-hydroxy-.gamma.-aminobutyryl) derivative of kanamycin A (U.S. Pat. No. 3,781,268 and J. Antibiotics, 25 (12), 695- 708 (1972) where the derivative is designated as BB-K8). In this vein, there have been synthesized 1-amino-substituted derivatives of various aminoglycosidic antibiotics which carry an (S)-.alpha.-hydroxy-.gamma.-aminobutyryl substituent (hereinafter referred to as L-HABA) or its homologue, an .alpha.-hydoxy-.omega.-aminoalkanoyl substituent as a side chain on the 1-amino group (see, for example, British Patent No. 1,426,908, U.S. Pat. No. 4,001,208 and J. Antibiotics, 26, ( 6) 351- 357 (1973)). These substituted derivatives principally fall within the category of 1-N-(S)-.alpha.-substituted-.omega.-aminoalkanecarboxylic acid derivatives. A new type of side chain which the parent aminoglycosidic antibiotics should carry as a substituent on the 1-amino group and which is effective to improve the antibacterial properties of the parent antibiotics had not been discovered until 1-N-ethylsisomicin was successfully prepared by a semi-synthetic process.